Combination Of Lapatinib With Carboplatin, Paclitaxel, and With or Without Trastuzumab In Metastatic Breast Cancer.

NCT00367471 | Completed Phase 1 FDA Drug

• 2 other identifiers: EGF103892CLAP016A2102
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to determine the optimally-tolerated regimens (OTR) for lapatinib in combination with paclitaxel, carboplatin with and without trastuzumab in patients with metastatic breast cancer.

Conditions

Neoplasms, Breast

Keywords

metastatic; paclitaxel; lapatinib; trastuzumab; carboplatin; breast cancer

Outcome Measures

Primary Outcomes (1)

• Adverse events and safety evaluations

  * The OTR for Treatment Group A (lapatinib, paclitaxel, carboplatin, and trastuzumab) will be defined as the maximum dose level at which no more than one subject out of six experiences a dose-limiting toxicity (DLT) after completing one treatment cycle. * The OTR for Treatment Group B (lapatinib, paclitaxel, carboplatin) will be defined as the maximum dose level at which no more than one subject out of six experiences a DLT after completing one treatment cycle. * Adverse events and changes from baseline in laboratory values, Multiple-gated Acquisition (MUGA) scanning/Echocardiogram (ECHO), and vital signs will be evaluated to assess safety and tolerability.

  28 days

Secondary Outcomes (3)

• Tumor response by RECIST version 1.0

  From date of randomization until the date of first documented progression or death from any cause,whichever came first, assessed up to 48.5 months

• Duration of Response (DOR)

  From date of randomization until the date of first documented progression or death from any cause,whichever came first, assessed up to 48.5 months

• Progression-free survival (PFS)

  From date of randomization until the date of first documented progression or death from any cause,whichever came first, assessed up to 48.5 months

Study Arms (2)

Group A

ACTIVE COMPARATOR

Subjects in Treatment Group A (in cohorts of three) will receive oral lapatinib QD (Days 1 to 28). Following lapatinib administration on Day 1, paclitaxel will be administered intravenously over one hour followed immediately by an IV infusion of carboplatin over not less than 15 minutes. Carboplatin will be followed by an initial loading dose of trastuzumab by 90 minute IV infusion (first dose only) with subsequent IV doses of trastuzumab to be given weekly over 30 minute infusion. Doses of paclitaxel and carboplatin will be administered weekly (Day 1, 8, and 15). Trastuzumab is administered on Day 1, 8, 15, and 22. Treatment cycles are repeated every four weeks.

Drug: lapatinib; Drug: carboplatin; Drug: trastuzumab; Drug: paclitaxel

Group B

ACTIVE COMPARATOR

Subjects in Treatment Group B (in cohorts of three) will receive oral lapatinib QD (Days 1 to 28). Following lapatinib administration on Day 1, paclitaxel will be administered intravenously over one hour followed immediately by a ≥15 minute intravenous infusion of carboplatin. Doses of paclitaxel, and carboplatin will be administered weekly (Day 1, 8, and 15) for three weeks with cycles repeated every four weeks.

Drug: lapatinib; Drug: carboplatin; Drug: paclitaxel

Interventions

lapatinib DRUG

Lapatinib (GW572016) is a potent small molecule, reversible inhibitor of both EGFR and ErbB2 tyrosine kinases

Group A; Group B

carboplatin DRUG

An alkylating agent used in the treatment of some cancers

Group A; Group B

trastuzumab DRUG

A monoclonal antibody that interferes with the HER2/neu receptor

Group A

paclitaxel DRUG

A mitotic inhibitor used in cancer treatment

Group A; Group B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically- or cytologically-confirmed invasive breast cancer with Stage IV disease.
• Treatment Group A: Documentation of ErbB2 status (IHC 3+ or FISH+) in breast tumor specimens must be demonstrated before study enrollment. It is requested that archived breast tumor tissue be sent to a central laboratory for independent confirmation of ErbB2 status by FISH analysis.
• Treatment Group B: Documentation of ErbB2 status (IHC or FISH) in breast tumor specimen must be demonstrated before study enrollment. It is requested that archived breast tumor tissue be sent to a central laboratory for independent confirmation of ErbB2 status (FISH analysis).
• Subjects must be ≥18 years of age.
• Male or female
• Criteria for female subjects:
• Non-child-bearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are post-menopausal defined as no menstruation for more than 12 months);
• Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility.) This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate. These subjects must have a negative serum pregnancy test at screening and agree to one of the following:
• Complete abstinence from intercourse from two weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; or
• Consistent and correct use of one of the following acceptable methods of birth control:
• male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject;
• implants of levonorgestrel;
• injectable progestogen;
• any intrauterine device (IUD) with a documented failure rate of less than 1% per year;
• oral contraceptives (either combined or progestogen only); or

You may not qualify if:

• Subject has peripheral neuropathy of Grade 2 or higher;
• Subject has had prior systemic cytotoxic chemotherapy for metastatic or locally recurrent disease. Also, any subjects with prior chemotherapy in the adjuvant or neoadjuvant setting with anthracycline or anthracenedione-containing regimens with cumulative doses of ≥ 360mg/m2 of doxorubicin, ≥ 720mg/m2 of epirubicin, or ≥ 72 mg/m2 of mitoxantrone. Patients with prior hormonal therapy(ies) are eligible.
• Subjects with prior systemic investigational drugs within the past 30 days or topical investigational drugs within the past seven days;
• Subjects with uncontrolled or symptomatic angina, arrhythmias.
• Subjects with Class II to IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
• Subjects with a known immediate or delayed hypersensitivity or untoward reaction to paclitaxel, trastuzumab, carboplatin, or other related compounds, or to drugs chemically related to lapatinib. These include other aminoquinazolines , such as gefitinib (Iressa), erlotinib (Tarceva), or other chemically-related compounds.
• Has malabsorption syndrome, a disease affecting gastrointestinal function, or resection of the stomach or small bowel.
• Subjects taking any prohibited medications as per protocol.
• Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Novartis Investigative Site

La Jolla, California, 92093-0987, United States

Location

Novartis Investigative Site

Indianapolis, Indiana, 46202, United States

Location

Novartis Investigative Site

Greensboro, North Carolina, 27403, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Lapatinib; Carboplatin; Trastuzumab; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2006
• First Posted: August 23, 2006
• Study Start: December 7, 2006
• Primary Completion: December 22, 2010
• Study Completion: September 12, 2019
• Last Updated: September 9, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)